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Content current as of October 12, 2026. AI-assisted draft; not yet reviewed by a licensed pharmacist. Current CDC schedules: immunization schedules.
- The disease and why it matters
- Video and figures
- Get CE credit
- Products available
- Who should get it
- Dosing and schedule, including catch-up
- Administration
- Storage and handling
- Contraindications and precautions
- Safety and adverse events
- Special populations
- Counseling pearls for the pharmacy counter
- Common patient questions
- References
The disease and why it matters
CDC says smallpox is a very serious disease caused by variola virus that can spread from person to person, while monkeypox (mpox) is a rare disease with symptoms similar to but milder than smallpox that can nonetheless cause death; vaccinia virus can cause disease when people are exposed to recently vaccinated people (for example after ACAM2000) or to infected animals. [1]
Routine vaccination against smallpox in the United States ended in the 1970s; for specific populations at high risk of occupational exposure to orthopoxviruses, the 2015 ACIP recommends routine vaccination, and CDC's mpox page says monkeypox vaccines are expected to be protective regardless of clade or subclade. [2] [3]
Video and figures
Video
Get CE credit
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Products available
Two vaccines are licensed in the United States for orthopoxvirus prevention: JYNNEOS (Bavarian Nordic), a third-generation vaccine based on a live, attenuated, non-replicating Modified Vaccinia Ankara (MVA) virus, and ACAM2000 (Emergent), a second-generation live vaccinia virus vaccine that replicates efficiently in humans and has more side effects and contraindications; only JYNNEOS has been used in recent outbreaks. [3]
| Vaccine | Manufacturer (FDA page) | FDA-approved use | Route and dose |
|---|---|---|---|
| JYNNEOS | Bavarian Nordic A/S [4] | Prevention of smallpox and mpox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection [5] | Subcutaneous; two 0.5 mL doses 4 weeks apart [5] |
| ACAM2000 | Emergent Product Development Gaithersburg Inc. [6] | Active immunization for the prevention of smallpox and mpox disease in individuals determined to be at high risk for smallpox or mpox infection [7] | Percutaneous by scarification: a droplet (approximately 0.0025 mL) picked up with a bifurcated needle and administered with 15 jabs [7] |
CDC says JYNNEOS is fully licensed for subcutaneous administration in individuals 18 years and older and became commercially available in the U.S. in April 2024; ACAM2000 and JYNNEOS are the only two licensed smallpox vaccines, and the Strategic National Stockpile also holds the investigational Aventis Pasteur Smallpox Vaccine (APSV), which could be used in a smallpox emergency only under an IND or EUA. [3] [2]
The FDA JYNNEOS page is marked content current as of 05/14/2025 and the label posted on it shows a placeholder date ("MM/YYYY"); the FDA ACAM2000 page is marked content current as of 05/12/2026, and its label highlights list a recent major change (indications, mpox disease) of 8/2024. [4] [5] [6] [7]
Who should get it
CDC / ACIP (mpox vaccine page, September 4, 2026)
As of September 4, 2026
ACIP recommends the 2-dose JYNNEOS series for pre-exposure vaccination of people at risk for occupational exposure to orthopoxviruses (as an alternative to ACAM2000) and for people aged 18 years and older at risk of monkeypox during an outbreak, including travelers to countries with ongoing human-to-human transmission of clade I MPXV who anticipate sex with a new partner, sex at a commercial sex venue, sex in exchange for money, goods, drugs or other trade, or sex in association with a large public event; and for gay, bisexual and other men who have sex with men, and transgender or nonbinary people, who in the past 6 months had a new diagnosis of at least 1 sexually transmitted disease, more than one sex partner, sex at a commercial sex venue, or sex in association with a large public event in an area where transmission is occurring, plus their sexual partners and people who anticipate these situations. CDC does not recommend routine immunization of the general public. [3]
CDC smallpox vaccine page (November 6, 2024)
As of November 6, 2024
The 2015 ACIP recommendations advise routine vaccination of laboratory personnel who directly handle cultures of, or animals infected with, replication-competent vaccinia virus, recombinant vaccinia viruses derived from replication-competent vaccinia strains, or other orthopoxviruses that can infect humans (for example monkeypox, cowpox and variola); routine vaccination is not recommended for, but should be offered to, healthcare personnel who treat or anticipate treating patients with vaccinia virus infections and anyone administering ACAM2000. [2]
JYNNEOS is not recommended as a routine vaccination for healthcare personnel unless sexual risk factors are present, and clinical laboratory personnel in hospitals who handle blood, urine and other bodily fluids from patients are not recommended to receive vaccination at this time, whereas certain research and diagnostic laboratorians who work with orthopoxviruses are recommended to receive vaccination and booster doses. [3]
Post-exposure: vaccine should be given as soon as possible, ideally within 4 days of exposure, and vaccination 4 through 14 days after exposure may still provide some protection; after 14 days clinicians should consider benefits case by case; vaccination after onset of signs or symptoms, after a diagnosis or after recovery is not expected to provide benefit. [3]
Dosing and schedule, including catch-up
| Regimen | Route | Volume | Doses | Interval |
|---|---|---|---|---|
| Standard, ages 18 years and older | Subcutaneous | 0.5 mL | 2 | 28 days (4 weeks) [3] |
| Standard, younger than 18 years (under EUA) | Subcutaneous | 0.5 mL | 2 | 28 days (4 weeks) [3] |
| Alternative, ages 18 years and older (under EUA) | Intradermal | 0.1 mL | 2 | 28 days (4 weeks) [3] |
CDC says there is currently adequate supply so clinicians can preferentially use the subcutaneous route; the second dose may be given up to 7 days later than the minimum interval (up to 35 days after dose 1); there is no need to restart or add doses if the interval is extended; a dose may be given up to 4 days before 28 days (a grace period of a minimum of 24 days after the first dose); the dosing regimens are interchangeable. [3]
JYNNEOS route: CDC compared with the label
As of September 4, 2026
CDC says the standard regimen (0.5 mL subcutaneous) is the FDA-approved dosing regimen and that an alternative intradermal 0.1 mL regimen for people 18 and older, and subcutaneous dosing for people younger than 18, are authorized under an Emergency Use Authorization issued in August 2022. [3]
FDA label (JYNNEOS)
As of May 14, 2025
The label gives subcutaneous administration of each 0.5 mL dose and a 2-dose schedule 4 weeks apart, for adults 18 years of age and older. [5]
ACAM2000 is given as a single percutaneous dose by the multiple-puncture technique; the 2015 ACIP recommendations call for routine vaccination of specified laboratory personnel, and the label requires training on safe and effective administration and provision of a Medication Guide and instructions on vaccination-site care. [2] [7]
Boosters: CDC web page compared with the VIS
As of September 4, 2026
CDC's mpox page says boosters are not currently recommended except for certain people who work with orthopoxviruses in research or diagnostic laboratories; booster doses every 2 to 3 years have always been recommended for certain laboratory and healthcare workers at occupational risk, and CDC does not recommend boosters for those vaccinated during the 2022 clade IIb outbreak; ACIP did not believe available data supported an additional dose in immunocompromised people. [3]
CDC VIS (January 31, 2025 edition)
As of January 31, 2025
The VIS says JYNNEOS is usually given as 2 injections 4 weeks apart, people who received smallpox vaccine in the past might need only 1 dose, and booster doses are recommended every 2 or 10 years if a person remains at continued risk for exposure to smallpox, monkeypox or other orthopoxviruses. [1]
CDC cites effectiveness estimates from studies since 2022 of 35% to 86% for 1 dose and 66% to 90% for 2 doses, and says peak immunity is expected 14 days after the second dose; infections after 2 doses have typically been milder. [3]
Administration
- JYNNEOS: inspect the milky, light yellow to pale white suspension for particulate matter and discoloration and do not administer if present; administer each 0.5 mL dose subcutaneously (typically over the triceps in people 12 months and older, or anterolateral thigh in infants younger than 12 months, per CDC); intradermal administration involves injecting between the epidermis and hypodermis, typically on the volar forearm. [5] [3]
- JYNNEOS is supplied in a one-vial presentation (yellow cap) that does not require reconstitution and a two-vial presentation in which the lyophilized antigen (yellow cap) must be reconstituted with the diluent (blue cap) before administration. [5]
- JYNNEOS typically may be administered without regard to timing of most other vaccines, including influenza vaccine on the same day at different anatomic sites if possible; there is no required minimum interval from COVID-19 vaccines, though adolescent or young adult men recommended to receive both might consider waiting 4 weeks because of the observed myocarditis and pericarditis risk with ACAM2000 and COVID-19 vaccines and hypothetical risk with JYNNEOS, unless at increased risk. [3]
- ACAM2000: the vaccinia virus is transmissible and should be handled as an infectious agent once vials are open; replication-competent vaccine can be transmitted from the vaccine recipient to unvaccinated close contacts, so the vaccination site requires special care to prevent the virus from spreading. [7] [2]
Storage and handling
- JYNNEOS one-vial presentation: keep frozen at −25 to −15 °C (−13 to +5 °F) in the original package to protect from light; do not re-freeze a vial once thawed; once thawed it may be kept at 2 to 8 °C (36 to 46 °F) for 4 weeks; do not use after expiration. [5]
- JYNNEOS two-vial presentation: store the lyophilized antigen refrigerated at 2 to 8 °C in the original package to protect from light; store the diluent at room temperature (20 to 25 °C) or refrigerated; after reconstitution use immediately or store refrigerated at 2 to 8 °C, away from light, for up to 12 hours, and do not freeze. [5]
- ACAM2000: the lyophilized antigen is shipped frozen and stored in a freezer (average −25 to −15 °C); it may be stored refrigerated at 2 to 8 °C for up to 18 months or until expiry, whichever comes first; the diluent is stored at 15 to 30 °C; after reconstitution it may be stored refrigerated for up to 30 days and kept at 20 to 25 °C for up to 8 hours. [7]
Contraindications and precautions
| Vaccine or topic | Statement |
|---|---|
| ACAM2000 label | Contraindicated in individuals with severe immunodeficiency (for example bone marrow transplantation or primary or acquired immunodeficiency requiring isolation). [7] |
| ACAM2000 risks | Serious complications include myocarditis and/or pericarditis (approximately 5.7 per 1000 primary vaccinations), encephalitis, progressive vaccinia, generalized vaccinia, severe vaccinial skin infections, erythema multiforme major, eczema vaccinatum, ocular vaccinia that may lead to blindness, and fetal death; risks are increased with cardiac disease, eye disease treated with topical steroids, immune deficiency, eczema or other skin conditions, infants younger than 12 months, and pregnancy. [7] |
| JYNNEOS label | Persons who had a severe allergic reaction after a previous dose or exposure to a component may be at increased risk and the risk should be weighed against the risk of disease; immunocompromised persons, including those receiving immunosuppressive therapy, may have a diminished immune response. [5] |
| Infants younger than 6 months | VIGIV should be considered in lieu of JYNNEOS; clinicians should first contact their jurisdictional health department. [3] |
Safety and adverse events
JYNNEOS solicited reactions in smallpox vaccine-naive healthy adults (more than 10%): injection-site pain (84.9%), redness (60.8%), swelling (51.6%), induration (45.4%) and itching (43.1%), and systemically muscle pain (42.8%), headache (34.8%), fatigue (30.4%), nausea (17.3%) and chills (10.4%); frequencies in adults with HIV infection or atopic dermatitis were generally similar. [5]
ACAM2000: common adverse reactions include inoculation-site signs and symptoms, lymphadenitis and constitutional symptoms (malaise, fatigue, fever, myalgia, headache); inadvertent inoculation at other sites (most commonly face, nose, mouth, lips, genitalia and anus) is the most frequent complication. [7]
Syncope has been reported following vaccination with JYNNEOS and procedures should be in place to avoid injury from fainting; CDC lists local side effects (erythema, pain, edema, pruritus, hyperpigmentation, induration) and systemic side effects (fatigue, headache, myalgias, nausea, chills, fever), and says local side effects may be more severe with intradermal than subcutaneous administration. [5] [3]
Special populations
Pregnancy: available human data on JYNNEOS in pregnant women are insufficient to determine vaccine-associated risks, animal studies showed no evidence of harm, and CDC says JYNNEOS can be offered to pregnant or breastfeeding women who are otherwise eligible after discussing risks and benefits using shared clinical decision-making; breastfeeding is not a contraindication; the label likewise says available human data are insufficient to inform vaccine-associated risks in pregnancy. [3] [5]
ACAM2000 in pregnancy: it has not been studied in pregnant women, can cause fetal vaccinia and fetal death based on historical use of live vaccinia vaccines, is not recommended in pregnant women in non-emergency situations, and vaccinees should avoid becoming pregnant (or getting their partner pregnant) for 6 weeks after vaccination and until the vaccination site has healed. [7]
Immunocompromised and skin conditions: people with congenital or acquired immune deficiency, including those taking immunosuppressive medications and people with HIV regardless of immune status, should receive 0.5 mL subcutaneously; studies in people with atopic dermatitis showed immunogenicity with no concerning safety signals; people with a history of keloid scars are vaccinated as indicated; previous smallpox vaccination probably provides some protection but it may not be lifelong. [3]
Counseling pearls for the pharmacy counter
- JYNNEOS is made using weakened live vaccinia virus and cannot cause smallpox, monkeypox or any other infectious disease. [1]
- Evaluate and counsel patients with a comprehensive, non-judgmental social and sexual history, allowing individuals to self-attest vaccine eligibility without having to specify which criterion they meet. [3]
- Peak immunity is expected 14 days after the second dose, no vaccine is 100% effective, and two doses provide the best protection. [3]
- For ACAM2000, counsel on vaccination-site care and avoiding contact because the vaccinia virus can be transmitted to close contacts, including household members who are pregnant, immunocompromised or have eczema. [7] [2]
Common patient questions
A man at risk for mpox had one JYNNEOS dose 3 months ago and missed dose 2. Restart?
No. CDC says if the second dose is not given during the recommended interval it should be given as soon as possible, with no need to restart or add doses. [3]
Is a booster needed for someone vaccinated in 2022?
No. CDC does not recommend booster doses for those vaccinated during the clade IIb outbreak that began in 2022 or for the general population; boosters are recommended for certain laboratory workers at occupational risk. [3]
A person was exposed 10 days ago. Is vaccination still useful?
Vaccination 4 through 14 days after exposure may still provide some protection; ideally vaccine is given within 4 days. [3]
Which vaccine is preferred for a patient with HIV?
CDC says JYNNEOS is administered as 0.5 mL subcutaneous for people with immune deficiency, including HIV regardless of immune status, and ACAM2000 is contraindicated in severe immunodeficiency and has more side effects and contraindications. [3] [7]
Can JYNNEOS be given with the flu shot?
Yes. CDC says JYNNEOS typically may be administered without regard to timing of most other vaccines, including influenza vaccine on the same day at different anatomic sites if possible. [3]
References
- Centers for Disease Control and Prevention. Smallpox/monkeypox vaccine (JYNNEOS): what you need to know. Vaccine Information Statement, January 31, 2025. Accessed October 12, 2026. https://www.cdc.gov/vaccines/hcp/current-vis/smallpox-monkeypox.html. Accessed October 12, 2026.
- Centers for Disease Control and Prevention. About smallpox vaccines (health care providers). Page dated November 6, 2024. Accessed October 12, 2026. https://www.cdc.gov/smallpox/hcp/vaccines/index.html. Accessed October 12, 2026.
- Centers for Disease Control and Prevention. Vaccine for monkeypox prevention in the United States (health care providers). Page dated September 4, 2026. Accessed October 12, 2026. https://www.cdc.gov/monkeypox/hcp/vaccine-considerations/index.html. Accessed October 12, 2026.
- U.S. Food and Drug Administration. JYNNEOS product page (content current as of 05/14/2025). Accessed October 12, 2026. https://www.fda.gov/vaccines-blood-biologics/jynneos. Accessed October 12, 2026.
- JYNNEOS (smallpox and monkeypox vaccine, live, non-replicating), suspension for subcutaneous injection: prescribing information as posted on FDA's product page (revision date shown as a placeholder, "MM/YYYY"). Bavarian Nordic A/S. U.S. Food and Drug Administration. Accessed October 12, 2026. https://www.fda.gov/media/131078/download?attachment. Accessed October 12, 2026.
- U.S. Food and Drug Administration. ACAM2000 product page (content current as of 05/12/2026). Accessed October 12, 2026. https://www.fda.gov/vaccines-blood-biologics/vaccines/acam2000. Accessed October 12, 2026.
- ACAM2000 (smallpox [vaccinia] vaccine, live), for percutaneous use by scarification: prescribing information (labeling dates shown as "[10/2024]" and recent major changes 8/2024). Emergent Product Development Gaithersburg Inc. U.S. Food and Drug Administration. Accessed October 12, 2026. https://www.fda.gov/media/75792/download?attachment. Accessed October 12, 2026.
For professional education. Check current labeling and guidance before acting. Not medical advice.
